Is it safe to administer TNKase (tenecteplase) outside of its approved time window?

Safety of TNKase Administration Outside the Approved Time Window

TNKase (tenecteplase) should not be administered outside its approved time window except in specific circumstances where the benefits may outweigh the risks, such as in symptomatic STEMI patients presenting >12 hours after symptom onset with large areas of myocardium at risk or hemodynamic instability when PCI is unavailable. 1

For Acute Myocardial Infarction (STEMI)

Established Time Windows

• The benefits of fibrinolytic therapy, including TNKase, are well-established within 12 hours of symptom onset for STEMI patients, with greater benefit observed in those who present early after symptom onset 1
• The benefit of fibrinolytic therapy in STEMI patients who present >12 hours after symptom onset has not been established 1

Limited Exceptions for Late Administration

• In symptomatic STEMI patients presenting >12 hours after symptom onset, TNKase may be considered if:
  • There is a large area of myocardium at risk 1
  • The patient has hemodynamic instability 1
  • Primary PCI is unavailable 1

Contraindications Remain Critical

• Absolute contraindications to TNKase must be strictly observed regardless of timing, including:
  • Any prior intracranial hemorrhage 1
  • Known structural cerebral vascular lesions 1
  • Known malignant intracranial neoplasms 1
  • Ischemic stroke within 3 months 1
  • Active bleeding or bleeding diathesis 1
  • Suspected aortic dissection 1

For Acute Ischemic Stroke

Current Evidence

• For acute ischemic stroke, the evidence for tenecteplase outside the standard 4.5-hour window is mixed and evolving 2, 3
• The TRACE-III trial showed that tenecteplase administered 4.5 to 24 hours after stroke onset in patients with large-vessel occlusion resulted in less disability compared to standard medical treatment, but with higher rates of symptomatic intracranial hemorrhage (3.0% vs 0.8%) 2
• However, the TIMELESS trial found that tenecteplase initiated 4.5 to 24 hours after stroke onset in patients with middle cerebral artery or internal carotid artery occlusions did not result in better clinical outcomes than placebo 3

Risk-Benefit Assessment

• The risk of symptomatic intracranial hemorrhage increases when thrombolytics are administered outside approved time windows 2, 3
• Patient selection using advanced imaging to identify salvageable tissue may help identify those who could benefit from extended window treatment 4, 2, 3

Clinical Decision Making

For STEMI:

• Primary PCI remains the preferred reperfusion strategy for STEMI, especially beyond the 12-hour window 1
• If PCI is not available and the patient presents >12 hours after symptom onset:
  • Assess for ongoing symptoms suggesting continuing ischemia 1
  • Evaluate the extent of myocardium at risk 1
  • Consider the patient's hemodynamic stability 1
  • Carefully review all contraindications 1

For Stroke:

• Current guidelines do not recommend routine use of tenecteplase outside the established time windows for stroke 1
• Clinical trials are ongoing to better define the role of tenecteplase in extended time windows 4

Key Pitfalls to Avoid

• Administering TNKase outside approved windows without careful patient selection increases bleeding risk, particularly intracranial hemorrhage 1, 2
• Failing to transfer patients to PCI-capable centers after fibrinolytic therapy, even when administered in extended windows 1
• Overlooking absolute contraindications when considering extended window treatment 1
• Not considering the higher bleeding risk in elderly patients when administering thrombolytics outside standard windows 1

In summary, while there may be specific circumstances where TNKase administration outside the approved time window could be considered, this decision must be made with extreme caution, weighing potential benefits against significant risks, and should generally be avoided unless specific high-risk features are present and alternative treatments are unavailable.